Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Minimum audible angle, just noticeable interaural differences and speech intelligibility with bilateral cochlear implants using clinical speech processors

Sound localization and speech intelligibility were assessed in 5 patients implanted bilaterally with Medel C40+ or Medel C40 cochlear implant (CI) systems. The minimum audible angle (MAA) around the head in the horizontal plane was assessed in patients with bilateral CI using white noise bursts of 1000 ms duration presented from a loudspeaker mounted on a rotating boom and compared with the MAA of age-matched normal hearing controls. Spatial discrimination was found to be good in front and in the back of the head with near-normal MAA values (patients: 3-8 degrees , controls: 1-4 degrees ). In contrast, poor performance on the sides was found (patients: 30 to over 45 degrees , controls 7-10 degrees ). Bilateral CI significantly improved spatial discrimination in front for all patients, when compared with the use of either CI alone. Just noticeable differences (JNDs) in interaural intensity and time were assessed using white noise bursts (1000 ms duration; 50 ms linear ramp). In addition, interaural time JNDs were assessed using click trains (800 ms duration, 40 mus clicks, 50 Hz) and noise bursts in which either only the envelope or only the fine structure was shifted in time. In comparison with normal hearing controls, patients with bilateral CI showed near-normal interaural intensity JNDs but substantially poorer interaural time JNDs depending on the type of stimulus. In contrast to envelope onset/offset cues, interaural fine structure time differences were not perceived by the patients using CI systems employing the continuous interleaved sampling strategy without synchronization between their pulse stimulation times. Speech intelligibility in quiet and CCITT noise from the side (+/-90 degrees ) was assessed using the German HSM sentence test and was significantly better when using bilateral CI in comparison with either unilateral CI, mainly due to a head shadow effect. These favorable results are in agreement with the patients' subjective experiences assessed with a questionnaire and support the use of bilateral CI

Petrous bone cholesteatoma removal with hearing preservation

Clinical and radiologic outcome analysis after petrous bone cholesteatoma (PBC) removal with simultaneous functional reconstruction

Bilateral cochlear implantation and directional multi-microphone systems

Better speech understanding in noise is a common goal of bilateral cochlear implantation and directional multi-microphone systems. In this study, the performance of five signal processing/presentation strategies is compared: (1) monaural presentation using a single omnidirectional microphone, (2) monaural presentation using a simple two-microphone beamformer in a behind-the-ear (BTE) housing, (3) monaural presentation using a complex four-microphone adaptive beamformer, (4) binaural presentation using two omnidirectional microphones and (5) binaural presentation using two simple two-microphone beamformers in separate behind-the-ear units

Human temporal bones versus mechanical model to evaluate three middle ear transducers

A life-size mechanical middle ear model and human temporal bones were used to evaluate three different middle ear transducers for implantable hearing aids: the driving rod transducer (DRT), the floating mass transducer (FMT) or vibrant sound bridge, and the contactless transducer (CLT). Results of the experiments with the mechanical model were within the range of the results for human temporal bones. However, results with the mechanical model showed better reproducibility. The handling of the mechanical model was considerably simpler and less time-consuming. Systematic variations of mounting parameters showed that the angle of the rod has virtually no effect on the output of the DRT, the mass loading on the cable of the FMT has a larger impact on the output than does the tightness of crimping, and the output level of the CLT can be increased by 10 dB by optimizing the mounting parameters

Prospektive Studie zur Evaluation des Restgehörserhalts nach Cochlea-Implantation

Mit zunehmender Präzisierung der chirurgischen Technik und durch die Einführung atraumatischer Elektroden ist es in den vergangenen Jahren möglich geworden, eine CochleaImplantation unter Erhaltung eines vorbestehenden Restgehörs durchzuführen. Ziel dieser Arbeit war es, den Restgehörerhalt und das postoperative Sprachverstehen quantitativ zu erfassen und mit den Resultaten früherer CIOperationen ohne Restgehörserhalt zu vergleichen

Retrograde cochlear implantation in postmeningitic basal turn ossification

Postmeningitic basal turn ossification is a challenge for successful cochlear implantation despite the availability of sophisticated implants and advanced drill-out procedures. A less complex concept consisting of a cochleostomy near the apex with retrograde array insertion is evaluated clinically and experimentally with emphasis on imaging of intracochlear array morphology

An international otology database

There are many reports in the literature on the outcome of ear surgery. However, it is difficult to make comparisons from these reports because of a lack of uniformity in the way in which outcomes are reported. At the same time, the general public expects doctors to provide them with information regarding the benefits and risks of surgery. Many ear surgeons will not be able to provide this information because few have an up-to-date database. A group of otologists in Europe has attempted to establish a common otology database. The aim is to create a framework whereby surgeons in Europe can contribute to a common ear database using a web-based system. The proposed methodology involves two levels of data entry. Level 1 is a minimal database where the main outcomes are included. Level 2 is a comprehensive database where detailed information on pathologies, risk factors, and surgical procedures is also recorded. As both databases share the same core data, clinicians using database 1 can still compare their outcomes with those using database 2. Clinicians will be able to input and retrieve ear data onto or from the web-based database. There has already been an international consensus on the content of the common ear database. The website address is www.ear-audit.net. The international project has now been in operation for more than 6 months, and Ear UK has already given its endorsement. The founder members include 27 otologists from 12 European countries. The cumulative outcome from this group of surgeons will be used as the benchmark for the purpose of comparative audit. These benchmark sites will be subjected to regular external validation. The web-based system is interactive and gives instant feedback to individual surgeons who wish to compare their results to the benchmark. Therefore, it can be a good learning tool for trainees or less experienced surgeons. The common data entry system also provides an opportunity for clinicians to collaborate in clinical researc